{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:18:10Z","timestamp":1785766690082,"version":"3.56.0"},"reference-count":21,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T00:00:00Z","timestamp":1651449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2022,10]]},"abstract":"Abstract<\/jats:title>Dapagliflozin improves glycemic control in patients with type 2 diabetes mellitus (T2DM) and is approved in Japanese patients with type 1 diabetes mellitus (T1DM) with inadequate glycemic control. The objectives of this work were to characterize the dapagliflozin pharmacokinetics (PK) in patients with T1DM, assess the influence of covariates on dapagliflozin PK, and compare dapagliflozin systemic exposure between patients with T1DM and T2DM. Population PK analysis was performed using a nonlinear mixed\u2010effect modeling approach. The analysis included 5793 dapagliflozin plasma concentrations from 1150 adult patients with T1DM (global population), who were on routine insulin therapy, collected from 1 phase 2 (NCT01498185) and 2 phase 3 (DEPICT\u20101, NCT02268214; DEPICT\u20102, NCT02460978) studies. Covariate effects were investigated using stepwise covariate modeling. Model\u2010derived area under the concentration\u2010time curve (AUC) in patients with T1DM was compared to AUC in patients with T2DM (using data from historical dapagliflozin studies). The final 2\u2010compartmental model adequately described the dapagliflozin concentrations in patients with T1DM. The estimated apparent clearance was 20.5 L\/h. Renal function (measured as estimated glomerular filtration rate), sex, and body weight were identified as covariates, where patients with better renal function, male patients, and heavier patients had lower dapagliflozin systemic exposure. Among the covariates studied, none of the covariates affected dapagliflozin systemic exposure >1.4\u2010fold compared to a reference individual and were therefore deemed to be not clinically relevant. Dapagliflozin systemic exposure was comparable between patients with T1DM and T2DM.<\/jats:p>","DOI":"10.1002\/jcph.2062","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T05:58:44Z","timestamp":1649656724000},"page":"1227-1235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Dapagliflozin Pharmacokinetics Is Similar in Adults With Type 1 and Type 2 Diabetes Mellitus"],"prefix":"10.1002","volume":"62","author":[{"given":"Johanna","family":"Melin","sequence":"first","affiliation":[{"name":"Clinical Pharmacology & Quantitative Pharmacology Clinical Pharmacology & Safety Sciences R&D AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Tang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology & Quantitative Pharmacology Clinical Pharmacology & Safety Sciences R&D AstraZeneca Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinko","family":"Reki\u0107","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology & Quantitative Pharmacology Clinical Pharmacology & Safety Sciences R&D AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengt","family":"Hamr\u00e9n","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology & Quantitative Pharmacology Clinical Pharmacology & Safety Sciences R&D AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Penland","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology & Quantitative Pharmacology Clinical Pharmacology & Safety Sciences R&D AstraZeneca Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Boulton","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology & Quantitative Pharmacology Clinical Pharmacology & Safety Sciences R&D AstraZeneca Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Parkinson","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology & Quantitative Pharmacology Clinical Pharmacology & Safety Sciences R&D AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.021887"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30308-X"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0623"},{"key":"e_1_2_11_5_1","unstructured":"FARXIGA\u00ae (dapagliflozin) US [prescribing information].Wilmington DE: AstraZeneca Pharmaceuticals LP;2014."},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12638"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2013.07.002"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2013.06.017"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0104-3"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.20"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13664"},{"key":"e_1_2_11_12_1","volume-title":"StatPearls [Internet","author":"Sapra A","year":"2022"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12594"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-2955"},{"key":"e_1_2_11_15_1","unstructured":"Center for Drug Evaluation and Research.Clinical Pharmacology and Biopharmaceutics Review(s).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2014\/202293Orig1s000ClinPharmR.pdf. 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